This invention relates to soft tissue implants and more particularly to soft tissue implants with a micron-scale surface texture to optimize anchorage of the implant in the tissue bed.
The reaction of living tissue to an implant can take a number of different forms. For example, the initial response to the surgical trauma of implantation is usually called the acute inflammatory reaction and is characterized by an invasion of polymorphonuclear leukocytes (PMNs). The acute inflammatory reaction is followed by the chronic inflammatory reaction, which is characterized by the presence of numerous macrophages and lymphocytes, some monocytes and granulocytes. Fibroblasts also begin accumulating in the vicinity of the implant and begin producing a matrix of collagen. The macrophages attempt to phagocytize the implant. However, if the implant is too large to be engulfed by the macrophages and is of a material resistant to digestion by the macrophages, these macrophages fuse together to form multinucleate foreign body giant cells, hereafter referred to simply as giant cells. Macrophages and giant cells are the most common type of cell around many types of implants. The fibroblasts and collagen form a connective tissue capsule around the implant and the chronic inflammatory cells to effectively isolate the implant and these cells from the rest of the body. Connective tissue consisting of a fine network of collagen with active producing fibroblasts accompanied by chronic inflammatory cells, capillaries and blood vessels is referred to collectively as granulation tissue.
Thus, when a material is implanted into a soft tissue bed of a living organism such as a human or an animal, a granulation tissue capsule is formed around the implant material consisting of inflammatory cells, immature fibroblasts and blood vessels. This tissue capsule usually increases in thickness with time and contracts around the implant, deforming the implantation site, and possibly the implant itself depending upon the rigidity of the implant.
When an optimally biocompatible material is implanted, it elicits the formation of a thin and stable connective tissue film covering the implant surface with minimal involvement of inflammatory tissue components such as macrophages and giant cells. It is well documented in the biomaterials literature that bulk chemistry, electrochemical surface phenomena, surface geometry, and implant shape are factors determining the local histological response (histocompatibility) in the implantation site.
When the implant is porous with pore entry diameters larger than 20 microns, tissue grows into these pores. This phenomenon appears desirable to many investigators because in theory it allows tissue ingrowth into the implant and reduces capsular contraction. For example, U.S. Pat. No. 4,011,861 to Enger discloses an implantable electric terminal which has pores preferably in the range of about 10 to 500 microns so that blood vessels and tissue can grow into the pores. Similarly, MacGregor (U.S. Pat. No. 4,374,699) discloses a rigid implant having pores sized from 1 to 1,000 microns to allow penetration by blood cells. MacGregor also discloses a flexible polymeric implant having pores sized less than 20 microns to allow ingrowth by soft tissue.
However, our analytical studies of the ingrowing tissues revealed granulation tissue in these pores. This granulation tissue consisted of predominately inflammatory cells, relatively few fibroblasts decreasing in number with implantation time, and very immature extracellular connective tissue components. This chronic inflammatory tissue is highly undesirable since it represents a locus minoris resistentiae, and it appears to prevent the formation of mature connective tissue which is the optimal tissue for implant anchorage. See Schreuders et al. "Normal Wound Healing Compared to Healing within Porous Dacron Implants," J. Biomed. Mat. Res., 1988.
Eskin et al, "Endothelial Cell Culture on Dacron Fabrics of Different Configurations," J. Biomed. Mat. Res., volume 12, pages 517-524 (1978), reports on tests conducted with Dacron knits, velours, and felt, in which the filaments comprising all of the materials were about 10.0 microns in diameter. Endothelial cells appeared unable to bridge spaces between filaments and strands of yarn of greater than 20-30 microns. The bridging occurred only where the strands of yarn were contiguous or nearly so, and the cells did not grow into the interior of the yarn, but stayed on its surface. Moreover, the cells did not grow over each other. It was noted that vascular smooth muscle cells are able to bridge distances between filaments in Dacron velours measuring up to 500 microns. It was suggested that different properties between endothelial cells and smooth muscle cells might account for the different behaviors.
In Wasfie et al, "Inhibition of Epithelial Down-growth on Percutaneous Access Devices in Swine: II," volume XXX, Trans Am Soc Artif Intern Organs. pages 556-560 (1984) and Freed et al. "Long-term Percutaneous Access Device," volume XXXI, Trans Am Soc Artif Intern Organs, pages 230-232 (1985), the researchers describe a Percutaneous Access Device (PAD) designed to form a seal between it and the surrounding tissue to inhibit epidermal downgrowth and prevent resulting infection. The implant neck of the surface of the PAD is rendered "nanoporous," which means according to these researchers that it has pores which average 1.0 micron in diameter and 20 microns in depth. The pores are non-intercommunicating and are produced at a density of 15,000 per mm.sup.2. As shown in FIG. 3a of Wasfie et al. this pore density means that separations between pores can measure ten (10) microns or more. In developing their design for a stable PAD, they sought to inhibit epithelial migration and prevent entry of bacteria by mechanically stabilizing the PAD so as to protect the device-tissue interface from applied forces. The PAD is coated with autologous dermal fibroblasts using cell culture techniques under in vitro conditions that favor fibroblast proliferation followed by in vitro collagen synthesis and polymerization. The in vitro cell culture technique allows the autologous dermal fibroblasts to interlock firmly with the "nanoporous" surface, before the percutaneous implant is surgically inserted in vivo. i.e., into the living organism. The result of the in vitro cell culturing technique on the nanoporous surface is an Autologous, Living, Coated, Nanoporous surface, which is referred to as an ALCON surface. The PAD with the ALCON surface is then implanted in vivo into various living hosts such as swine, sheep, and humans. FIGS. 3a, 3b, and 4 of Wasfie et al show fibroblast cytoplasmic extensions protruding into pores of the "nanoporous" Lexan surface of the PAD neck. The Wasfie et al researchers believe that these cells are the original fibroblasts used to coat the implant surface in vitro to form the ALCON surface.
As reported in Freed et al, the swine ALCON surface implants had a PAD failure rate of one every 82 implant-months compared to a control failure rate of one every seven implant-months for PAD implants without the in vitro pre-implantation coating of autologous dermal fibroblasts. According to Freed et al, the failure rate of the ALCON surface implants shows promise as an effective means for transferring pneumatic power to an implanted heart system and as potentially useful for continuous ambulatory peritoneal dialysis and other therapies. However, the implants lacking the in vitro ALCON surface failed far sooner than conventional percutaneous implant devices.
Chehroudi et al, "Effects of a Grooved Epoxy Substratum on Epithelial Cell Behavior in vitro and in vivo," Journal of BioMedical Materials Research, Vol. 22, pp. 459-473 (1988), tested the hypothesis that contact guidance can be used to control epithelial migratory behavior with a study conducted in vitro and in the more complex in vivo environment. Epoxy resin structures having a smooth portion and a portion with V-shaped grooves measuring 10 microns deep, 17 microns across the top, and separated by flat ridges 22 microns wide, were implanted in rats. The report concludes that more epidermal cells attached to the grooved portion of the epoxy substrata than to the smooth portion. The epidermal cells interdigitated into the grooves of the grooved portion of the implant. The report concluded that the grooved substrata used in the study do not decrease and probably increase cell attachment. The absence of interconnecting pores which might facilitate infection was noted as an advantage of the epoxy substrata.